Chronic Aluminum Intake Causes Alzheimer’s Disease:

Applying Sir Austin Bradford Hill’s Causality Criteria

J.R. Walton∗
Faculty of Medicine, University of New South Wales, St George Hospital, Sydney, Australia

Journal of Alzheimer’s Disease 40 (2014) 765–838 DOI 10.3233/JAD-132204 765
Review Accepted 20 December 2013


Industrialized societies produce many convenience foods with aluminum additives that enhance various food properties
and use alum (aluminum sulfate or aluminum potassium sulfate) in water treatment to enable delivery of large volumes of
drinking water to millions of urban consumers. The present causality analysis evaluates the extent to which the routine, life-long
intake, and metabolism of aluminum compounds can account for Alzheimer’s disease (AD), using Austin Bradford Hill’s nine
epidemiological and experimental causality criteria, including strength of the relationship, consistency, specificity, temporality,
dose-dependent response, biological rationale, coherence with existing knowledge, experimental evidence, and analogy. Mechanisms
that underlie the risk of low concentrations of aluminum relate to (1) aluminum’s absorption rates, allowing the impression
that aluminum is safe to ingest and as an additive in food and drinking water treatment, (2) aluminum’s slow progressive uptake
into the brain over a long prodromal phase, and (3) aluminum’s similarity to iron, in terms of ionic size, allows aluminum to
use iron-evolved mechanisms to enter the highly-active, iron-dependent cells responsible for memory processing. Aluminum
particularly accumulates in these iron-dependent cells to toxic levels, dysregulating iron homeostasis and causing microtubule
depletion, eventually producing changes that result in disconnection of neuronal afferents and efferents, loss of function and
regional atrophy consistent with MRI findings in AD brains. AD is a human form of chronic aluminum neurotoxicity. The
causality analysis demonstrates that chronic aluminum intake causes AD.

Keywords: Aluminum, Alzheimer’s disease, amyloidogenesis, animal disease models, causality, disconnection, entorhinal cortex,
microtubules, neurofibrillary tangles, transferrin receptors